title: Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study.
abstract: OBJECTIVE
  We assessed the safety of the multikinase inhibitor regorafenib in patients with hepatocellular carcinoma (HCC) that had progressed following first-line sorafenib.
  
  
  METHODS
  Thirty-six patients with Barcelona Clinic Liver Cancer stage B or C HCC and preserved to mildly impaired liver function (Child-Pugh class A) received regorafenib 160 mg once daily in cycles of 3 weeks on/1 week off treatment until disease progression, unacceptable toxicity, death or patient/physician decision to discontinue. The primary end-point was safety; secondary end-points included efficacy (including time to progression and overall survival).
  
  
  RESULTS
  The median treatment duration was 19.5 weeks (range 2-103). At data cutoff, three patients remained on treatment. Reasons for discontinuation were adverse events (n=20), disease progression (n=10), consent withdrawal (n=2) and death (n=1). Seventeen patients required dose reductions (mostly for adverse events [n=15]); 35 patients had treatment interruption (mostly for adverse events [n=32] or patient error [n=11]). The most frequent treatment-related adverse events were hand-foot skin reaction (any grade n=19; grade ≥3 n=5), diarrhoea (n=19; n=2), fatigue (n=19; n=6), hypothyroidism (n=15; n=0), anorexia (n=13; n=0), hypertension (n=13; n=1), nausea (n=12; n=0) and voice changes (n=10; n=0). Disease control was achieved in 26 patients (partial response n=1; stable disease n=25). Median time to progression was 4.3 months. Median overall survival was 13.8 months.
  
  
  CONCLUSIONS
  Regorafenib had acceptable tolerability and evidence of antitumour activity in patients with intermediate or advanced HCC that progressed following first-line sorafenib.
authors.affiliation: BCLC Group Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain. Electronic address: jbruix@clinic.ub.es.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Tak
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Ho-Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mazzaferro
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
authors.forename: María
authors.initials: M
authors.lastname: Reig
authors.forename: Andrea
authors.initials: A
authors.lastname: Wagner
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001208:Asia; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib
keywords: Hepatocellular carcinoma; Receptor kinase inhibition; Regorafenib; Safety; Second line; Tolerability